The characteristics of the transition states for enzymic and non-enzymic chemical reactions will be determined and compared, primarily through the use of kinetic isotope effects, although other mechanistic methodology will also be employed. The reactions to be studied are mainly acyl-transfer and hydrogen-transfer processes. The enzymes involved include amidohydrolases, such as glutaminases and asparaginases, proteases such as trypsin and related systems, dehydrogenases, and aminotransferases. The isotope effects to be studied include secondary deuterium and primary carbon and oxygen effects for acyl transfer, solvent isotope effects for all reactions, primary and secondary deuterium and tritium effects for aminotransferase reactions and primary and secondary hydrogen effects for dehydrogenase reactions. Theoretical methods will be employed to explore structures and force fields for acyl-transfer and other transition states. Vibrational analysis methods will be used to assist in the interpretation of kinetic isotope effects of all kinds.